Research

My
interests are in the area of integrative and behavioural neuroscience: How do
neuronal mechanisms generate adaptive behaviour? How does dysfunction of
these mechanisms contribute to neurological and neuropsychiatric diseases?

From rapid memory encoding to
adaptive behaviour – functional differentiation and integration in the
hippocampus

Focusing
on the hippocampus, my research is concerned with the brain mechanisms
mediating memory and other behavioural functions, such as emotional, motivational,
and sensorimotor functions, and, especially, the integration of these diverse
functions. Combining behavioural testing with the manipulation and analysis
of brain function in rats, I study hippocampal functions, the underlying
mechanisms and connectivity, and the consequences of hippocampal dysfunction
that characterises many neuropsychiatric populations.

Functional-anatomical model of the hippocampus:
implications for behaviour in health and disease

My research is led by the idea (see
Bast
T, 2007, Rev Neurosci; Bast,
2011, Curr Opin Neurobiol) that the hippocampus integrates (i) anatomical
and physiological substrates of certain types of rapid information encoding
(including functional connectivity to entorhinal cortex) with (ii) direct
links (via prefrontal cortex and subcortical sites) to behavioural control functions,
such as emotional, motivational, executive, and sensorimotor processes (see
figure). Thereby, in humans and other mammals, normal
hippocampal function may enable rapid place and episodic(-like) learning
(i.e., encoding of events and their spatio-temporal context), and the
translation of such learning into behaviour. Examples of such behaviour
include our returning to where we parked our car or placed our key this
morning, or a rat’s returning to where it found food or safe refuge on a
previous occasion. On the other hand, permanent hippocampal damage may result
in striking and specific memory deficits, as reported in the famous case
studies of H.M. and other patients; furthermore, hippocampal dysfunction, as
found in schizophrenia, mood, and anxiety disorders, may, apart from memory
deficits, also contribute to other functional impairments, including aberrant
emotional, motivational, sensorimotor and executive functions.

Research methods

To study brain, especially hippocampal, substrates of
complex behaviour, I have been combining sophisticated behavioural testing
with brain manipulation and analysis in rats. Main approaches include:

·Selective neuropharmacological
(intracerebral microinfusions) and brain-lesion (cytotoxic lesions, fibre
cuts) techniques to manipulate (i) specific components of the hippocampal
circuitry and their interaction and (ii) cortical and subcortical structures
connected to the hippocampus.

·In vivo electrophysiology, in vivo
microdialysis, anatomical techniques, and, most recently, in vivo MRI
to characterise the pathways and mechanisms underlying the behavioural
significance of the different components of the hippocampal circuitry.

Functional significance
of hippocampal and prefrontal disinhibition in schizophrenia: integrative in vivo studies in rat models

Disinhibition, i.e. impaired inhibitory GABA transmission,
in the prefrontal cortex and hippocampus has emerged as key feature of schizophrenia
pathophysiology (see here). In current work, led with Marie Pezze, we examine if and how prefrontal and
hippocampal disinhibition disrupt cognition and behaviour. To this end, we
study the neural-network effects and behavioural/cognitive deficits resulting
from such disinhibition in rodent models. The work on hippocampal
disinhibition is guided by hypotheses based on the functional-anatomical
model of the hippocampus described above (see Bast, 2011, Curr Opin Neurobiol).

It is firmly established that the hippocampus is required
for certain types of everyday learning, including place learning, and we have
achieved remarkable insights into the underlying neural mechanisms of
information encoding and storage. However, how is, for example, place memory
translated into appropriate behaviour, such as returning to that place? A key
idea is that this translation may require interactions of the hippocampus
with brain sites playing central roles in behavioural control, such as
prefrontal cortex and subcortical sites, including striatum (Bast, 2011, Curr Opin Neurobiol). Consistent with this idea, we
provided evidence that the direct translation of rapid place learning into
behavioural performance depends on a region of the hippocampus where neural
substrates of accurate place encoding converge with links to prefrontal and
subcortical sites (Bast
et al, 2009, PLoS Biol). In current work, we aim to determine which
prefrontal and subcortical sites contribute to the learning-behaviour
translation and how the hippocampus interacts with these sites.

PhD
Students

PhD
Opportunities

The School
of Psychology awards
ca. 8 PhD
studentships (ca. £13,000 living allowance p.a. plus Home/EU student
fees) each academic year. If you are interested in the research
and projects outlined above and would like to work towards a PhD in this
area, please contact me well in advance of the mid-February deadline for
School Studentship applications. Suitable candidates would typically have some
relevant research experience (e.g., from undergraduate or MSc projects).